Treatment fluid multi-stream blood warmer

ABSTRACT

The disclosed subject matter relates to extracorporeal blood processing or other processing of fluids. A blood treatment system treats blood with multiple fluids and performs fluid balancing on a patient&#39;s blood compartment. Multiple streams influence the patient temperature but only a subset of the fluids are dynamically temperature regulated. The system regulates a temperature of the flow, for example, of dialysate in order to regulate the return temperature of blood, in such a way that the temperature effect of the multiple streams is compensated.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. national stage filing under 35 U.S.C. § 371of International Application No. PCT/US2017/066431 filed Dec. 14, 2017,which claims the benefit of U.S. Provisional Application No. 62/434,075,filed Dec. 14, 2016, all of which are hereby incorporated by referencein their entireties.

BACKGROUND

A basic function of many extra corporeal blood treatment systems (ECBTsystems), including hemodialysis, hemofiltration, hemodiafiltration,apheresis systems, etc., is the maintenance of the overall fluid balancebetween the fluid added to the patient and the fluid withdrawn from thepatient. Ideally, this exchange will result in a net loss or gain offluid to/from the patient that precisely matches the patient's treatmentrequirement. To achieve this, the ECBT may employ a volumetric fluidbalancing system, of which a variety of different types are known. Forexample, see U.S. Pat. Nos. 5,836,908, 4,728,433, 5,344,568, 4,894,150,and 6,284,131, each of which is hereby incorporated by reference as iffully set forth in their entireties herein.

Fluid balancing mechanisms generally attempt to ensure that the totalmass or volume of fluid pumped into, and removed from, the non-bloodside of a filter or dialysis are equal. To provide for a desireddifferential between the net quantity removed/added, the inflow andoutflow rates can be controlled to produce a net difference. This may beprovided by regulating the relative flow rates provided by ingoing andoutgoing pumps or by using a separate bypass, driven by a separate pump.In an example, such a bypass pump pumps at an ultrafiltration (“UF”)line rate which is added to the balanced withdrawal rate.

Gravimetric systems that balance flow by weighing mass from a source andcollected fluid from the treatment device and comparing the two areknown. Another approach is to measure incremental volume transfer. Hardplumbed or disposable lined balance chambers alternately fill and emptyin a manner that assures equal and opposite volume exchange. Systemsusing this approach are balancing a single inlet fluid flow with aneffluent stream. A second stream of fluid is frequently added to theextracorporeal circuit using an additional pump, or external IV pump.The volume of this second stream may be balanced by the isolatedultrafiltration (UF) pump in an attempt to maintain patient fluidbalance. This approach is limited by the calibration inaccuracies of theadditional or external pump and the isolated UF pump. These inaccuraciesare acceptable at low flow rates. However, at higher flow rates thecumulative volumetric inaccuracies may not achieve the desired patientvolumetric balance. Additionally, this approach requires an operator toindependently set the pump rates to achieve the desired balance.

Another function provided by extracorporeal blood treatment systems isthe maintenance of blood temperature of the patient under treatment.Such extracorporeal blood treatments fall into a variety of categoriesranging from blood oxygenation and therapeutic hypothermia to renalreplacement therapies such as hemodialysis (HD). In extracorporeal bloodtreatments, such as HD, blood is pumped from a patient through a bloodcircuit and through a treatment device, such as a dialyzer. Toxins andelectrolyte exchange across a dialyzer membrane to exchange with atreatment fluid. The exchange causes the removal of waste products inthe blood and excess water. A substantial volume of the patient's bloodmay pass through an extracorporeal blood treatment system during thecourse of a treatment such that any heat transfer to or from the bloodcan upset the patient's body temperature.

SUMMARY

The disclosed subject matter described in this disclosure includesapproaches to volumetric fluid balance using multiple volumetric orfixed-displacement pumps to control inflows and outflows from anextracorporeal circuit that have corresponding pump rates synchronizedrelative to each other to assure balanced flow rates. Techniques formaintaining patient blood temperature during treatment with multiplefluid streams while ensuring safe handling of blood are addressed.

In certain systems, volumetric fluid balancing may be performed for asingle therapy fluid stream using a system configuration includingbalance chambers, peristaltic pumps, and mechanically controlled pinchvalves. The therapy fluid entering the blood path of the extracorporealcircuit may be balanced with effluent removed from the blood paththrough the dialyzer of the circuit so that the patient volume is notaffected by this exchange of fluids. The limitation to a single therapyfluid inlet flow is a common limitation of various dialysis machinesthat use balance chambers. Some extracorporeal therapies can use morethan one therapy fluid inlet flow that may be volumetrically controlledto achieve an overall patient fluid balance. For example, the differencebetween the total fluid that moves into the patient (for example, byflowing into the patient's blood stream) and that withdrawn from thepatient must be precisely controlled. For example, in dialysistreatment, the amount of fluid entering the patient, for example throughpredilution, post-dilution, citrate infusion, and reverseultrafiltration streams may be balanced against the net ultrafiltrationstream to achieve a target net ultrafiltration rate. The subject matterdescribed in this disclosure provides machine configurations thatsupport one or more therapy fluid flows synchronized with the effluentfluid flow from the extracorporeal circuit to achieve accurate fluidbalance and the warming of fluid in such systems.

The disclosed subject matter includes several different systemconfigurations that support one or more therapy fluid inlet flowsbalanced with the effluent flow. In embodiments, reliable flow balanceis obtained by synchronizing the pump flows by various controlmechanisms. The temperature of the blood is maintained by adding heat toa subset of the treatment fluid streams such that heat is transferred tothe blood without creating a local temperature rise that might adverselyaffect the blood and so as to warm blood to a predefined temperature ofthe blood returned to the patient. To this end, the temperature of bloodin a venous line (blood return temperature) connected for return flow ofblood to the patient is continuously monitored and used for negativefeedback control. The set point of the blood return temperature can beestablished based on an estimate of the heat transfer from/to theenvironment between the point of the blood return temperaturemeasurement and the patient blood access (e.g., fistula needle, centralline, or dual needle access).

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will hereinafter be described in detail below with referenceto the accompanying drawings, wherein like reference numerals representlike elements. The accompanying drawings have not necessarily been drawnto scale. Where applicable, some features may not be illustrated toassist in the description of underlying features.

FIG. 1 shows a treatment fluid multi-stream blood treatment system thatregulates the flow of blood relative to a treatment fluid to generate acumulative target ratio of fluid drawn or infused into a patient overthe course of a treatment while maintaining a blood temperature.

FIG. 2A shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to embodiments of the disclosed subject matter.

FIG. 2B shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to further embodiments of the disclosed subject matter inwhich fluid balancing is performed in an alternative method and systemfrom that of FIG. 2A.

FIG. 3A shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to embodiments of the disclosed subject matter in which fluidbalancing is performed in a method and system like that of FIG. 2A and apartial feedforward method and system are used for temperatureregulation.

FIG. 3B shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to embodiments of the disclosed subject matter in which fluidbalancing is performed in the alternative method and system as in FIG.2B and temperature regulation includes a feed-forward method and systemas in FIG. 3A.

FIG. 4 shows a flow chart defining a controller-implemented method ofregulating venous return temperature in the presence of multiple fluidsthat affect the temperature as shown in the systems of FIGS. 2A and 2B,according to embodiments of the disclosed subject matter.

FIG. 5 shows a flow chart defining a controller-implemented method ofregulating venous return temperature in the presence of multiple fluidsthat affect the temperature as shown in the systems of FIGS. 3A and 3B,according to embodiments of the disclosed subject matter.

FIG. 6 shows a flow chart defining a controller-implemented method forobtaining a control input parameter during priming of a system and usedin the methods of FIGS. 3A and 3B, according to embodiments of thedisclosed subject matter.

FIG. 7 is a schematic diagram of the flow rates involved in the heat andmass balance of the blood treatment according to any of the embodimentsaccording to a specific example illustrating a method according to anyof the disclosed embodiments.

FIG. 8 illustrates temperature and flow changes in an exemplary model ofa blood treatment device according to embodiments of the disclosedsubject matter.

FIGS. 9A and 9B show systems that combine an external fluid source witha single or multiple-stream extracorporeal blood treatment device wherethe extracorporeal blood treatment device manages the patient bodytemperature by regulating the temperature of a subset of the streamsthat affect blood return temperature.

DETAILED DESCRIPTION

FIG. 1 shows a blood treatment system 100 that regulates the flow offluid in a fluid circuit 121 that includes an arterial blood line 139, avenous blood line 137, a fresh treatment fluid line 127 and a wastetreatment fluid line 125. In particular, the blood treatment system 100regulates the flow of blood relative to a treatment fluid to generate acumulative target ratio of fluid drawn or infused into a patient overthe course of a treatment or drawn or returned to a priming fluidsource/sink, respectively. The net flow of fluid into or out of apatient (priming fluid source/sink—hereafter any reference to “patient”and/or “blood” with reference to a synchronization mode orsynchronization operation may be replaced by priming fluid and/or acombination source and sink thereof, because the synchronizationmode/operation mode discussed herein can be done during priming with arecirculating or single-pass priming operation as well as during atreatment, as will be evident to the skilled artisan), at any giventime, is determined by a then-instant difference between the volume ofblood pumped from a treatment device 114 (labeled F for filter, forexample a dialyzer, a common embodiment) to the volume pumped into thetreatment device 114. Blood is pumped into the treatment device 114 byan arterial blood pump 110 and pumped from the treatment device 114 by avenous blood pump 104. The illustrated configuration is common fordialysis systems, and may include all the typical incidents thereof, butdiffers specifically in that there are two blood pumps: the arterialblood pump 110 and the venous blood pump 104.

During a treatment mode and also in embodiments of a synchronizationmode, blood is pumped to and from a patient access 122. In otherembodiments synchronization may be done instead with a priming fluid.During priming operations, the patient access or priming connector(s)may be connected to priming fluid source, sink, or recirculatingcontainer instead. Thus, 122 may be considered generally to represent apatient access connected to a patient, in which case the circulatingfluid is blood, or 122 may be considered to represent a priming fluidsource, sink, or recirculating container, in which case, the circulatingfluid is priming fluid.

Control and sensing are provided by a controller 140 which may be of anyform but typically some type of programmable digital controller, forexample, an embedded computer. A treatment fluid is pumped from atreatment fluid source 124 through an air detector 118 through thetreatment device 114, past a waste line clamp 130, to the drain 126(indicated by W for waste). Drain 126 may be a drain of a plumbingsystem or a collection container or any other device for disposal ofwaste treatment fluid. Treatment fluid 124 may be dialysate, replacementfluid, or any other medicament.

A replacement fluid 120 may be pumped into the arterial blood line 139or the venous blood line 137 through a replacement fluid line 135 or138, respectively (or both) for predilution, post-dilution or acombination of both. In alternative embodiments, the dilution may occurat a midpoint of the treatment device 114, for example by using a twosmaller units of a treatment device 114 that provides a junction betweenthem or by means of a special structure of the treatment device 114 thatprovides for mid-dilution. The treatment device 114 may be adapted for avariety of types of blood treatment that require balancing flows intoand out of a fluid circuit, including, but not limited to, dialysis,hemofiltration, hemodiafiltration, apheresis, adsorption, orhemoperfusion. These treatment modalities apply to all of the disclosedembodiments including those originally disclosed in the claims. Furthersupplemental fluids indicated by supplemental fluid 134 and supplementalfluid 132 may be pumped into the arterial blood line 139 by respectivepumps, namely, supplemental fluid pump 142 and supplemental fluid pump144, either or both of which may be present. Examples of supplementalfluids are drugs and anticoagulant (e.g., citrate, heparin).

Pressure sensors may be provided at various points throughout the fluidcircuit 121. In particular, an arterial pressure sensor 112 may detectpressure of the blood in the blood line 139 upstream of the arterialblood pump 110. In embodiments, each pump contributing to flow balancemay have a pressure sensor up stream of it to ensure that pressurecompensated control of its speed can be provided. For example, anadditional treatment fluid pump pressure sensor 119 may be provided. Inembodiments, pressure sensors used for pressure compensated speedcontrol are positioned such that they provide a reliable and consistentindication of pressure upstream of the respective pump or pumps. Thus,they may be positioned close or at least such that there are nointervening possible interferences such as tube lengths that couldbecome kinked. A blood inlet pressure sensor 108 may detect pressure ofthe blood in the arterial blood line 139 downstream of the arterialblood pump 110 and upstream of the treatment device 114. A blood outletpressure sensor 106 may detect pressure of the blood in the venous bloodline 137 upstream of the venous blood pump 104 and downstream of thetreatment device 114. A venous blood pressure sensor 102 may detectpressure in the venous blood line 137 downstream of the venous bloodpump 104 and upstream of the patient access 122. The controller 140receives signals from each of the arterial pressure sensor 112, bloodinlet pressure sensor 108, blood outlet pressure sensor 106, and venousblood pressure sensor 102 as well as an air sensor 118 (also referred toas an air detector) that is positioned to detect air in the freshtreatment fluid line 127. The controller 140 is also connected tocontrol each of the arterial blood pump 110, venous blood pump 104,replacement fluid pump 116, supplemental fluid pump 142, andsupplemental fluid pump 144, as well the waste line clamp 130. Note thatthe waste line clamp 130 could be replaced by any type of valve thatselectively halts or permits flow or another pump.

In alternative configurations, instead of treatment fluid pump 128 andwaste line clamp 130 being used to halt flow as described below, a wastefluid pump may be provided in the position of waste line clamp 130,which can halt flow by halting rotation. In any of the embodiments,including the present and further embodiments to be described below ordescribed above, any element identified as a line or fluid line (orfluid circuit) could be any type of flow channel includinginterconnected tubes including pumping tube segments, channels formed ina cartridge (as a pattern of troughs sealed by an overlying weldedfilm), a pattern-welded pair of weldable sheets, a laminated stack ofelements that defines flow channels, or any other device that guides theflow of fluid. Any element identified as a pump may be any type of pumpor actuator that is volumetric aka, positive displacement type.Peristaltic pump is a type of a positive displacement pump. Suchembodiments of lines and fluid lines or fluid circuits may be disposableor otherwise replaceable components that engage pumps, sensors, andactuators of a treatment machine that includes such pumps, sensors, andactuators as identified in the embodiments. Such a machine may beillustrated schematically in the drawings, but not necessarily as aseparate component, for example a pump indicated by a single element mayinclude a pump actuator, e.g., a rotor, that works together with a pumptubing segment of a fluid circuit, while both are indicated by a pumpsymbol schematically in the drawing. Similarly, sensors and clamps arenot illustrated separately in all the drawings. Such a machine may beembodied in multiple separate components and may be generally describedas having a receiving adapter to allow the connection of a disposablefluid circuit.

The term, receiving adapter, or similar term is an abstraction that maycover all the various mechanisms that permit the operative associationbetween a permanent device and a disposable or replaceable componentwhich together form one of the apparatuses disclosed or claimed. Thisapplies to all the disclosed and claimed embodiments. For example, thedrawings described above and below illustrate a system which, whenconsidering that portions are replaceable, indicate the presence of ablood circuit receiving adapter and a medicament (treatment fluid,dialysate, or similar fluid) receiving adapter. The fluid circuits(including blood circuits) may include treatment components as well asportions that engage with sensors and actuators. Again, these commentsapply to all embodiments.

Any element identified as a pressure sensor may be a combination of afluid circuit portion such as a pressure pod or drip chamber and anelectronic transducer such as a strain gauge or displacement encoderconnected to an element such as a diaphragm that registers pressure. Theforegoing elements are well known classes of devices and furtherelaboration is not needed to permit the skilled reader to develop thedetails of working embodiments of the described subject matter. Fluidsmay be supplied from containers such as bags or inline fluid generatorssuch as used in dialysis clinics.

In a treatment operation of blood treatment system 100, arterial bloodpump 110 and venous blood pump 104 pump blood or priming fluid in thedirections indicated by the respective arrowhead of each pump symbol.They pump at rates controlled by the controller 140 to approximatelybalance (equivalently, “equalize”) the flow of blood in the arterialblood line 139 against the flow of blood in the venous blood line 137such that a net take-off of fluid (ultrafiltrate) or a net infusion offluid takes place (which may be called negative ultrafiltrate). Theinstantaneous rate of ultrafiltration refers to net loss of fluid by thepatient and negative ultrafiltration refers to net gain of fluid by thepatient. This is achieved through control of the total displaced volumeby the arterial pump 110 relative to the venous pump 104. Theultrafiltrate may be established by a predetermined ratio of the flowrates of the arterial 110 and venous 104 pumps if the transfer is spreaduniformly over the treatment interval or the net ultrafiltrate may beestablished in a discontinuous manner by varying the ratio of the flowrates of the arterial 110 and venous 104 pumps to achieve a cumulativeultrafiltrate. Thus, ultrafiltrate volume is established by the totalvolume transported by the venous pump 104 minus the total volumetransported by the arterial pump 110 over the course of a treatment.Ultrafiltrate rate may identify the instantaneous difference between therates of the venous 104 and arterial 110 pumps.

The controller 140 may be programmed to ensure that the net volume ofultrafiltrate or infused fluid meets a prescribed target which may bestored by the controller 140. The pumping speeds required to achievecommanded flow rates may be determined by the controller 140 using datastored by the controller such as look up tables or formulas. A commandedflow rate refers to the operational property (e.g., shaft speed of aperistaltic pump) that is under direct control of the controller whichcorresponds more or less accurately to a flow rate, conditions that mayvary from those used to establish a transfer function defining therelationship between the operational property and an actual flow rateproduced by it. The conditions may include manufacturing variabilitysuch as pumping tube segment and fluid line diameter, materialproperties of the pumping tube segment, pump lubrication, as well asfactors that change due to operation history and storage such asdistortions, material creep, etc. The ratio of flow rate to pump speedmay be presented by stored look-up table data to indicate target pumpspeeds by a relationship between pressure difference and flow rate.

Treatment fluid 124 is pumped by fresh treatment fluid pump 128 at apredefined rate stored in the controller 140, which rate may be selectedto correspond to the blood flow rate. The replacement fluid 120 may bepumped at a rate controlled by the controller 140 by controlling thecommanded rate of replacement fluid pump 116. The supplemental fluid 134may be pumped at a rate controlled by the controller 140 by controllingthe commanded rate of supplemental fluid pump 142. The supplementalfluid 132 may be pumped at a rate controlled by the controller 140 bycontrolling the commanded rate of supplemental fluid pump 144. Any ofthe replacement fluid 120, supplemental fluid 134, or supplemental fluid132 are optional and may or may not be included, along with therespective lines and pumps, in alternative embodiments.

Valves or pinch clamps identified anywhere in the current patentapplication may be of any type. For example, flexible membranes closedover cartridge-embedded ports, electrically actuated pinch clampsemploying linear actuators such as solenoid plungers or stepper motoractuators may be used. The particular type of valve mechanism does notlimit the disclosed subject matter. Line 136 is present to indicate thatin alternative embodiments, the supplemental fluids may enter thearterial blood line 139 upstream or downstream of the arterial bloodpump 110.

The return temperature of blood is continuously controlled andmaintained by the controller 140 in response to a venous returntemperature indicated by a venous return temperature sensor 105. Venousreturn temperature sensor 105 is positioned and configured to detect thetemperature of blood in the venous line and output a correspondingsignal to the controller. To control the venous return temperature, thecontroller 140 regulates the heat output (or if a net cooling isrequired the refrigeration level) of a thermal regulator 117 thatdeposits or withdraws heat to or from the treatment fluid in the freshtreatment fluid line 127. The thermal regulator 117 may be a fluidwarmer such as a direct contact thermoelectric heater. Alternatively itmay be a radiant heater that minimizes the creation of inducedelectrical current in fluid lines. The thermal regulator 117 may alsoprovide heat and cooling effect or only cooling effect. For example, itmay include a thermoelectric cooler such as a thermopile or peltiercooler or it may be vapor compression machine. The examples are notlimiting of the invention and any of them as well as others may becombined or substituted to provide alternative embodiments of a deviceto regulate the temperature of fluid in fresh treatment fluid line 127.All the sensors and actuators identified above may be connected to thecontroller 140 either by wired or wireless signal connection or throughfinal power drives.

As indicated above, in any of the embodiments, the fluid balance (netultrafiltrate volume) resulting from the flows to and from a patient isunderstood to accrue over a period of time. Thus, although in theembodiments, the controller is described as controlling pumping rates toachieve a fluid balance, optionally offset by a net transfer of fluid toor from the patient (net ultrafiltrate volume), it is understood thatthe pumping rates need not be constant, define a constant ratio overtime, or even define a smoothly varying ratio over time. Since theultimate goal is to control the total loss or gain of fluid from apatient (net ultrafiltrate volume), pumping rates can establish avariety of rates over time such that the cumulative effect is the targetultrafiltrate volume at the end of the treatment. Rates may be constantor vary step-wise, smoothly, and may result in a temporary gain of fluidby the patient during a portion of a treatment interval and net lossduring another portion to achieve a total gain or loss for the entiretreatment. For another example, the entire fluid gain or loss can beconfined to a single part of the treatment interval. The controller mayalso limit estimated ultrafiltrate so that overall balance does notexceed a certain volume at a given time. A rate of ultrafiltration mayalso, or alternatively, be limited by the controller.

Referring to FIG. 2A, a blood treatment system 200A has a bloodtreatment machine 208 which engages with a (preferably disposable) fluidcircuit that includes a blood line 203 and treatment fluid lines201A-201E. Blood is pumped by a blood pump 220. For example, the bloodpump may be a peristaltic pump. Fluid pumps 210, 212, 214, 216, and 218engage with treatment fluid lines 201A-201E, respectively to pumptreatment fluids in and out of the fluid circuit. Specifically, forexample, a treatment fluid conveyed by treatment fluid line 201A may bea post-dilution fluid, drug, or other medicament, which flows directlyand is admixed with blood after the blood flows through a treatmentdevice 204 which may also be part of the fluid circuit. Anothertreatment fluid may flow through treatment fluid line 201B, pumped byfluid pump 212, into the treatment device 204 and out through treatmentfluid line 201C, pumped by treatment fluid pump 214. The difference inflow rates of the treatment fluid pump 212 and treatment fluid pump 214determines a net rate of addition or loss of fluid to or from the pump.Thus, in this embodiment, the fluid balance of the patient will bedetermined and controlled by regulating the relative speeds of treatmentfluid pump 212 and treatment fluid pump 214.

The treatment device 204 transfers heat to or from the treatment fluidcirculating through treatment fluid line 201B and treatment fluid line201C. The treatment fluid line 201B has a temperature regulator 206 towarm or cool, depending on whether the blood is to be heated or cooled.The temperature regulator may be of any of the types of fluid warmers orrefrigerators used for temperature regulation. Preferably it isthermostatically regulated to limit the temperature of fluid leaving itto a predefined range. The power output of the temperature regulator 206is controllable by the controller 202 which is connected to receive atemperature signal from the blood return temperature sensor 222indicating the temperature of blood returning to the patient throughblood line 203. The controller generates an error input from adifference between the blood return temperature and a predeterminedvalue. It regulates the power output of the temperature regulator 206,for example by negative feedback control. The latter may be achieved bya digital proportional, integral, proportional-integral, orproportional-integral-differential algorithm, for example. Thecontroller may be configured to limit the temperature at which atreatment fluid contacts blood to a predefined range of temperature. Forexample, the fluid may be limited to the range 30-42 C at all times andbetween 28-46 C for any time interval greater than 30 seconds.Temperature sensors may be provided on each of the treatment fluid linesto permit the controller to generate an alarm, reduce a rate of heatingor cooling of a medicament, and/or reduce or halt the flow of treatmentfluids if a range or range per time interval is exceeded.

Another treatment fluid may be conveyed by treatment fluid line 201D maybe a pre-dilution fluid, drug, or other medicament, which flows directlyand is admixed with blood before the blood flows through the treatmentdevice 204 and after the blood pump 220. The rate of flow throughtreatment fluid line 201D is regulated by the treatment fluid pump 216.Another treatment fluid may be conveyed by treatment fluid line 201E maybe a pre-dilution fluid, drug, or other medicament, which flows directlyand is admixed with blood before the blood flows through the treatmentdevice 204 and after the blood pump 220. The rate of flow throughtreatment fluid line 201E is regulated by the treatment fluid pump 216whose speed is controlled by the controller 202.

In FIG. 2A as well as FIGS. 2B, 3A, and 3B, 207 indicates a temperaturesensor that detects a respective fluid temperature that affects theblood return temperature. Temperature sensor 207 may be a contact typesensor that contacts the fluid channel or blood channel. An example of acontact type sensor is described in Patent Publication US20150204733 toNewell, et al. Other types of contact or wetted temperature sensors mayalso be used such as RFIDs, thermistors, or any type of temperaturesensor able to generate a signal indicating temperature. As discussedherein, the various blood return temperature control algorithms rely onone or more temperatures and the acquisition of these temperatures maybe done by any suitable means including by any of a variety ofparticular locations of the sensors with respect to fluid-conveyingchannels.

FIG. 2B shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to further embodiments of the disclosed subject matter inwhich fluid balancing is performed in an alternative method and systemfrom that of FIG. 2A. Referring now to FIG. 2B, the flow balance employsan arterial blood pump 220 and a venous blood pump 228 whose relativepumping speeds determines the rate of ultrafiltration. In the presentembodiment, a single treatment fluid pump 212 is used. The controlmethod of FIG. 4 may be used to regulate the power of temperatureregulator 206. In other respects the embodiment of FIG. 2B is the sameas the embodiment of FIG. 2A so the corresponding description is notrepeated.

It should be clear to those of skill in the art of extracorporeal bloodtreatment systems, from the foregoing description, that the contributionof thermal energy to blood in either of the systems 200A and 200Bdepends on a combination of admixing of all the treatment fluidsentering the system through treatment fluid lines 201A-201E as well asheat transfer between the blood and non-blood compartments of thetreatment device 204 which in part determines the exchange of thermalenergy between blood and the treatment fluid carried in treatment fluidlines 201B and 201C.

Referring now to FIG. 4 , a flow chart shows a controller-implementedmethod of regulating venous return temperature in the presence ofmultiple fluids that affect the temperature as shown in the systems 200Aand 200B, according to embodiments of the disclosed subject matter. Theprocedure starts at S10 with estimating the thermal power output of thetemperature regulator 206 to achieve a predefined blood returntemperature of the blood as indicated by the blood return temperaturesensor 222. This estimate may be standardized based on standardenvironment temperature or by data entered by a user through a userinterface indicating estimated temperature of the treatment fluidscarried respectively by the treatment fluid lines 201B and 201C and apredefined target magnitude of the blood return temperature which isstored by the controller either permanently as part of its programmingor via a prescription. The initial power required may also be stored asdetermined by a previous operation such as prior treatments which arecontrolled according to the present procedure for example. Theestimation may factor-in, using a heat transfer model, the initial flowrates of the treatment fluids and blood. A mass balance can be doneinitially to calculate the blood flow rate at each stage of the bloodtreatment process, illustrated schematically in FIG. 7 .

The mass balance for the first two stages of admixing are given bym _(B,2) =m _(B,1) +m _(F,1)  (1)m _(B,3) =m _(B,2) +m _(F,2)  (2)

where m_(B,i) is the mass flow rate of blood at the ith stage andm_(F,j) is the mass flow rate of jth treatment fluid at the jth stage.The mass flow of blood after the blood treatment device includes a netultrafiltration rate equal to the difference between the inflowing andoutflowing rates of the third treatment fluid. As indicated below, thereis also a pressure-gradient driven convection between blood andtreatment fluid compartments but this does not cause a net transfer offluid between the two compartments so the mass flow of blood remainsunaffected by this process.m _(B,4) =m _(F,4) −m _(F,3) +m _(B,3)  (3)

The mass balance for the final stage of admixing is given by equation 4.m _(B,5) =m _(B,4) +m _(F,1)  (4)

It will be clear to those of skill in the art that the above mass flowbalance pertains to the exemplary system and that other types of systemswould involve different algorithms and account for different effects.The example is not intended to be limit the scope of the teachings ofthe present disclosure. The same applies to the following thermal energybalance discussion.

The energy balances for the flow circuit depicted in FIG. 7 may beapplied backwards, proceeding from the target blood return temperatureT_(V) to calculate the blood temperature T_(B,4) at the inlet to thejunction where the fifth treatment fluid F5 flow is admixed with flowingblood, given by equation 6 by solving for T_(B,4) from the energybalance of equation 5.

$\begin{matrix}{{{m_{B,4}{c_{B}( {T_{V} - T_{B,4}} )}} + {m_{F\; 5}{c_{F\; 5}( {T_{V} - T_{F\; 5}} )}}} = 0} & (4) \\{T_{B,4} = \frac{{m_{F\; 5}{c_{F\; 5}( {T_{V} - T_{F\; 5}} )}} + {m_{B,4}c_{B}T_{V}}}{m_{B,4}c_{B}}} & (5)\end{matrix}$

Where c_(B) is the specific heat of blood, T_(Fi) is the ith treatmentfluid temperature, c_(Fi) is the ith treatment fluid specific heat, andT_(V) is the venous blood temperature.

The temperature of blood at the blood treatment device inlet T_(B,3) iscalculated from T_(B,1) by the admixing equation 6.

$\begin{matrix}{T_{B,3} = \frac{{m_{B,1}c_{B}T_{B,1}} + {m_{F\; 1}c_{F\; 1}T_{F\; 1}} + {m_{F\; 2}c_{F\; 2}T_{F\; 2}}}{{m_{B,1}c_{B}} + {m_{F\; 1}c_{F\; 1}} + {m_{F\; 2}c_{F\; 2}}}} & (6)\end{matrix}$

Referring to FIG. 8 , a common type of blood treatment, dialysis, isassumed for the sake of discussing temperature changes for an example.The approach can be modified to suit different types of treatments suchas hemofiltration or hemodiafiltration and other types of bloodtreatments. During dialysis, the ultrafiltration causes a net flow offluid from the blood to the treatment fluid compartment of the dialyzercausing a gain in mass volume between m_(F3) and m_(F4) with aconcomitant loss if mass volume between m_(B,3) and m_(B,4). Note thatthe flow directions are indicated by the arrows. Because of the changein pressure of blood flowing through the blood treatment device, theremay be a net transfer of fluid from blood compartment to the treatmentfluid compartment which does not affect the blood temperature but doesreduce the temperature of the treatment fluid while simultaneously thereis a net gain in temperature of the blood. After a certain point,because of decreasing pressure in the blood compartment as blood flowsthrough, at a later point in the blood treatment device, there may be anoffsetting flow from the treatment fluid compartment to the blood. As aresult, the mass flow of blood reaches a minimum of m_(B,A) and thenrises to m_(B,4), while the mass flow of treatment fluid initially dropsand then a minimum of m_(F,A) and then rises to m_(F4). The changes andrelative magnitudes are not to scale. There is also a heat gain byconvection across the membrane and near the blood outlet there isadditional heat added by admixing of treatment fluid causing additionaltemperature rise of the blood.

Dialyzers are complex heat exchangers and are difficult to model. Eventhe film coefficient on the surface of the membranes is effected by masstransport across the membrane. Practical ways to estimate thetemperature rise due to heat transfer from admixing and thermalconvection include an empirical function or a lookup table that show theinlet temperature difference T_(F3)−T_(B,3) for a given blood flow rate,treatment flow rate, and ultrafiltration rate. Such devices allow theestimation of (T_(F3)−T_(B,3))=F(UF, m_(F3), m_(B,3)), where UF is thefraction of the blood flow rate that is withdrawn into the treatmentfluid compartment as ultrafiltrate. Then T_(F3) can calculated and thepower required to raise the initial temperature T_(F,in) of treatmentfluid F3 prior to heating with temperature regulator 206 can becalculated from Q=m_(F3)c_(F3)(T_(F3)−T_(F,in)) giving an estimate asindicated in S10.

At S12, the flow of blood and fluids is started and the temperatureregulator 206 operated with the estimated power rate. At S14, the bloodreturn temperature is sampled and an error calculated from it based on astored target blood return temperature to adjust the power of thetemperature regulator 206 using a feedback control algorithm at S16. AtS18, the controller determines whether the fluid flow rates or bloodflow rate have been changed since the previous pass through S18. If oneof them has, by a respective predefined magnitude, then control revertsto S10 to estimate the power output for the temperature regulator 206.The change of conditions may include any of those parameters used forthe function described relative to S10, including a change inultrafiltration rate. If it is determined that the flow conditions areconstant, then at S20, it is determined whether the treatment has beenterminated, if not, control reverts to S14, otherwise the active controlof the temperature regulator 206 is terminated.

FIG. 3A shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to embodiments of the disclosed subject matter in which fluidbalancing is performed in a method and system like that of FIG. 2A and apartial feedforward method and system are used for temperatureregulation. Referring to FIG. 3A, a temperature sensor 2161 is connectedto the controller 202 and indicates the temperature of the fluid intreatment fluid line 201B that is applied to the treatment device 204.The temperature indication of the fluid applied to the treatment device204 is feedback controlled to a target temperature estimated to berequired for achieving the target blood return temperature rather thandirectly calculating the power required to obtain that temperature.Effectively this like setting a thermostat to regulate the power of thetemperature regulator 206.

FIG. 3B shows a simplified schematic of a multiple treatment fluidstream system that actively regulates temperatures of at least onestream and includes a controller and treatment device for blood,according to embodiments of the disclosed subject matter in which fluidbalancing is performed in the alternative method and system as in FIG.2B and temperature regulation includes a thermostatic device of FIG. 3A.

FIG. 5 shows a flow chart defining a controller-implemented method ofregulating venous return temperature in the presence of multiple fluidsthat affect the temperature as shown in the systems of FIGS. 3A and 3B,according to embodiments of the disclosed subject matter. Step S8represents an example of a priming procedure which is illustrated inmore detail in FIG. 6 . The priming procedure calculates UA, which isthe overall heat transfer coefficient, where U=heat transfer coefficientnormalized by area (W/m²K), and A is the area in m². The control flowproceeds as in the flow chart of FIG. 4 except that instead ofestimating the power output of the temperature regulator 206, a targettemperature of the fluid in treatment fluid line 201B and flowing intotreatment device 204 is calculated and used by the controller tofeedback-control the power of the temperature regulator 206 to achievethe target temperature of the fluid in treatment fluid line 201Bresponsively to the temperature indicated by temperature sensor 2161.This occurs at S36 in place of S10. The estimation may be done accordingto variety of methods implementable by a digital controller, for exampleas described above with reference to FIGS. 7 and 8 . At S30, thecontroller determines whether the temperature of the target temperatureof the fluid in treatment fluid line 201B is correct and if not,executes feedback control of the temperature regulator 206 at S32. Ifthe blood return temperature is within the stored predefined range atS30, then control proceeds to S38, where the target temperature for ofthe fluid in treatment fluid line 201B is adjusted by a feedbackalgorithm and stored by the controller based on the sampled venousreturn temperature. In other respects, the method of FIG. 5 is the sameas that of FIG. 4 .

FIG. 6 shows a flow chart defining a controller-implemented method forobtaining a control input parameter during priming of a system and usedin the methods of FIGS. 3A and 3B, according to embodiments of thedisclosed subject matter. Referring to FIG. 6 , a look up table orfunction provides (T_(F3)−T_(B,3))=F(UF, m_(F3), m_(B,3)) as describedabove. At S40, treatment fluid circuit including blood and treatmentfluid portions is primed. The priming fluid in the treatment fluidcircuit may serve as a model of blood. The configuration may includeactive cooling and heating of all fluids to permit any selectedtemperature of the blood and treatment fluids (which may also berepresented by priming fluid). At S44, the fluids are circulated for anarray of UF, mF₃, m_(B,3) values and the delta values T_(F3)−T_(B,3)recorded at S48 for each. The resulting set may be fitted to a look uptable or function S50 which is stored S52 for use during treatment.

FIGS. 9A and 9B show systems in which a separate source 302 ofintravenously-administered fluids is provided to a patient 325 throughan IV line 308 at a time of treatment by a blood treatment machine 304.Normally, IV line 308 would be connected directly to the patient, asshown in FIG. 9B, connected to optional IV line 331. In the foregoingembodiments, a blood return temperature that is effective to regulate apatient body temperature is shown to be maintained by regulating thetemperature of a treatment fluid that affects the blood returntemperature. Referring now to FIG. 9A, a blood treatment machine 304processes blood using one or more fluids 305. In the present embodiment,the blood treatment machine 304 consumes the one or more treatmentfluids 305 to treat the patient 325. One of the treatment fluids may beconsumed at a higher rate than the others, for example, dialysate orreplacement fluid for hemofiltration. That one fluid alone, or incombination with a subset of multiple fluids 305 may be heated by aheater 311 to regulate the temperature of return blood carried by avenous line 318 to regulate the temperature of the patient 325. Blood isdrawn from the patient 325 through arterial line 319 and returned to thepatient 325 through the venous line 318 after being treated. The bloodreturn temperature may be detected by a temperature sensor 309. Element306 is a fluid circuit support structure with sensors and actuators.

In addition, the patient 325 core temperature may be detected from thearterial blood temperature by a suitable positioned temperature sensorlike temperature sensor 309, in an embodiment. As described inInternational Patent Publication WO/2017/062923, a core temperaturemeasurement may be made by varying the heat transfer dynamics of a bloodcircuit and fitting parameters of a blood circuit heat transferconfiguration to measurements under the varied conditions. Then theinput temperature of the patient core can be extracted from the modeland a current temperature measurement remote from the patient core andoptionally other measurements such as blood flow rate. In a principalapplication, a patient's body temperature is calculated responsively toa temperature of blood flowing through a blood circuit taken at anextracorporeal blood treatment component. Blood flows into an arterialline in an extracorporeal blood circuit through one or more devices suchas a treatment device, and back to a patient. Body core temperature maybe calculated from a measured arterial blood temperature using a sensorthat is remote from the inlet. To do this, the temperature may bemeasured at multiple flow rates and temperature readings for eachcondition stored. Then these readings may be used with a thermal modelof the system to calculate the inlet temperature. In an embodiment, theheat transfer rate is the same for two flow rate conditions. This givestwo unknowns (the heat transfer rate) and two equations allowing theinlet temperature to be calculated from the remote temperature readingsand the flow rates, which are known. In embodiments this initialestimate of the inlet temperature can be improved by using an initialguess, estimate, or measurement of the ambient temperature torecursively calculate an improved estimate of the inlet temperaturewhich may be used again to improve it until converged. In otherembodiments the unknown parameters of inlet temperature heat transferrate (power units) may be calculated using a brute force optimizationmethod such as an annealing algorithm or Monte Carlo method. The lattermay be preferred where the fluid temperature is modeled as anexponential (decay), for example using log mean temperature difference(LMTD). In further embodiments, the ambient temperature may be estimatedby fitting three temperatures and three flow rates as knowns to athermal model of the flow system. Details of the core temperaturemeasurement method that may be applied to the present embodiments aredescribed in International Patent Publication WO/2017/062923.

The separate source 302 may be any type of intravenous fluid ormedicament treatment fluid that transfers heat to the venous bloodreturn through venous line 318 or which affect the temperature of adirectly connected patient 325. Note that direct connection to thepatient is not shown in FIG. 9A but a patient may be directly connectedby a separate line 331 instead of through the blood treatment machine304 as illustrated in both FIGS. 9A and 9B. Continuing to refer to FIG.9A, the through the blood treatment machine 304 functions as anintravenous fluid pump by metering intravenous fluid from the separatesource 302 using an internal pump (not shown) whose rate may becontrolled by a user interface (not shown separately but it should beclear the through the blood treatment machine 304 of FIGS. 9A and 9B maybe configured with a user interface 141 as described above in thedisclosure of the embodiments of FIGS. 1 through 3B. Blood treatmentmachine 304 pumps intravenous fluid at a rate commanded through the userinterface 141. The blood treatment machine 304 adjusts the temperatureof one or more of the fluids 305 to achieve the control goal of a targetcore temperature of the patient 325 or a target blood returntemperature. The intravenous fluid is admixed with blood in the samemanner as described with respect to the replacement and other fluids ofthe foregoing embodiments. The temperature of the intravenous fluid isindicated by a temperature sensor 307. The blood treatment machine 304controls the pump used to regulate the flow of intravenous fluid andtherefore, control by the blood treatment machine 304 may be responsiveto the temperature and flow rate of the intravenous fluid from thesource 302 in the manner described above with regard to the otherembodiments.

In the embodiment of FIG. 9B, a separate infusion pump 312 is controlledby its own user interface, but it sends indications of treatmentparameters to the controller 202 of the blood treatment machine 304 by asignal link 316, for example a conductive cable or a wireless link. Thetemperature of the fluid may be detected directly by the blood treatmentmachine 304 using a temperature sensor 307. Since the blood treatmentmachine thus has access to the flow rate and temperature, the disclosedcontrol method may be used to regulate the patient blood returntemperature. Note that in the embodiments of FIGS. 9A and 9B, theintravenous fluid is assumed to be admixed with blood at a pointupstream of the blood return temperature which is provided by thetemperature sensor 309. In the alternative embodiment of FIG. 9B inwhich the intravenous fluid is infused through a separate line 331, theblood treatment machine may provide an external temperature sensor 307′that may be attached to the separate line 331 to apply a temperaturesignal to the blood treatment machine controller 202. The externaltemperature sensor 307′ could be externally mounted or tethered to thetreatment machine and provide a temperature signal via a wired orwireless link 317 to the treatment machine.

In any of the embodiments, including the embodiments defined by theclaims, additional embodiments may be created by adding a feature inwhich the blood return temperature is controlled by negative feedbackcontrol loop responsively to the detected patient core temperature suchthat the control variable of blood return temperature is slaved to thepatient core temperature. The patient core temperature may be estimatedfrom the blood return temperature as discussed. The blood returntemperature required to achieve a target core temperature may becalculated based on data representing a model of the patient's thermalregulation requirements that has been customized for the patient. Thedata may be improved over time based on a continuous detection of coretemperature during a treatment. The blood return temperature may beslaved to the target core temperature as a feedback control loop. Thus,the control methods described above may be used to regulate a heater orcooler to adjust the treatment fluid temperature(s) to achieve a targetblood return temperature (venous blood temperature) and an outer controlloop may be implemented to adjust target blood return temperature toachieve a target core temperature. A net cooling or heating rate may bestored for the patient and used to establish an initial blood returntemperature target at the beginning of a successive treatment. The netcooling or heating rate may be normalized by room temperature byentering the room temperature in the user interface 141 or by directmeasurement of the room temperature. It may also be normalized by thetime of the treatment, time of last meal, type of meal (e.g., highprotein or low protein meal), or other factors that affect metabolicrate. Coefficients for each of these factors may be stored in a look uptable (LUT) each of whose entries corresponds to a respective answer toa question or a measurement indication (or range thereof). For example,the room temperature ranges may be respective entries in the LUT.Protein level of the most recent meal may be divided into some number oflevels, for example 3 corresponding to high protein, medium protein, orlow protein. Other examples may be readily determined by the skilleddesigner and need not be elaborated herein.

According to embodiments, the disclosed subject matter includesapparatus for controlling flow in a fluid circuit. A treatment machinewith flow regulators, a temperature regulator, and temperature sensorshas a controller connected to control the flow regulators and receivesignals from the temperature sensors to implement a therapeutictreatment by regulating the flow rates in each of multiple treatmentfluid lines and in each of arterial and venous blood lines of apredefined fluid circuit connectable in operative engagement with theflow regulators, the temperature sensors, and the temperature regulator.The predefined fluid circuit is of a type in which the arterial andvenous blood lines and at least some of the treatment fluid linestransfer heat and fluids between the treatment fluid lines and thearterial and venous blood lines. The controller is programmed to controlthe flow regulators to regulate respective flow rates in the treatmentfluid lines and the arterial and venous blood lines to produce apredetermined difference between flows in the arterial and venous bloodlines. The controller further is programmed to control the temperatureregulator to exchange heat with a subset of the multiple fluid lines toachieve a predefined temperature in the venous blood line.

In variations of the foregoing embodiment or embodiments, the subset isa single one of the multiple treatment fluid lines. In furthervariations of the foregoing embodiments, the single one is a dialysateor replacement fluid line. In the temperature regulator includes awarmer. In further variations of the foregoing embodiments, thetemperature sensors include a blood return temperature sensor thatindicates a blood return temperature and engages the venous blood lineand a temperature-regulator sensor that engages the single one of themultiple treatment fluid lines. In further variations of the foregoingembodiments, the controller is programmed to ensure that a temperatureof the fluid in the single one of the multiple treatment fluid linesremains below a predefined long term temperature at all times. Infurther variations of the foregoing embodiments, the controller isprogrammed to ensure that a temperature of the fluid in the single oneof the multiple treatment fluid lines remains at, or below, a predefinedlong term temperature at all times and at, or below, below a predefinedshort term temperature for no longer than a predefined short term timeinterval, whereby blood is not exposed to fluid at temperatures abovethe long or short term temperatures at any time or for longer than thepredefined short term time interval, respectively. In further variationsof the foregoing embodiments, the temperature sensors include multipletreatment fluid temperature sensors that engage the multiple treatmentfluid lines, respectively and wherein controller is programmed tocontrol the temperature regulator responsively to temperatures indicatedby the multiple treatment fluid sensors. In further variations of theforegoing embodiments, the controller is programmed to compensate for acombined effect of heating and/or cooling by fluid in the multipletreatment fluid lines on the blood return temperature. In furthervariations of the foregoing embodiments, the controller is programmed toensure that a temperature of the fluid in the single one of the multipletreatment fluid lines remains at, or below, a predefined long termtemperature at all times and at, or below, below a predefined short termtemperature for no longer than a predefined short term time interval. Insuch further variations, the controller is programmed to compensate fora combined effect of heating and/or cooling by fluid in the multipletreatment fluid lines on the blood return temperature and thetemperature of the fluid in the single one of the multiple treatmentfluid lines.

According to embodiments, the disclosed subject matter includes a methodof regulating a blood return temperature during a blood treatment. Themethod includes withdrawing blood from a living subject andsimultaneously cooling and heating the blood by admixing of one or moreof at least two treatment fluids, withdrawing fluid from the blood, andtransferring heat between the blood and the one or more of the at leasttwo treatment fluids. The method includes returning the blood to theliving subject after the simultaneously heating and cooling anddetecting a temperature of the returning blood. The method includesusing the controller connected to receive a signal indicating thetemperature of the returning blood and responsively thereto, regulatinga rate of heat addition or withdrawal to or from one of the at least twotreatment fluids by means of a temperature regulator controlled by thecontroller to achieve a predefined temperature of the returning blood.

In variations of the foregoing embodiments, the regulating a rate ofheat addition or withdrawal is responsive to respective flow rates ofthe at least two treatment fluids. In further variations of theforegoing embodiments, the regulating a rate of heat addition orwithdrawal is responsive to a combined effect of the simultaneouslycooling and heating. In further variations of the foregoing embodiments,the regulating a rate of heat addition or withdrawal is responsive to isrespective flow rates of the at least two treatment fluids. In furthervariations of the foregoing embodiments, the one of the at least twotreatment fluids is a dialysate. In further variations of the foregoingembodiments, the one of the at least two has a higher flow rate than oneor more others of the at least two. In further variations of theforegoing embodiments, the regulating a rate of heat addition orwithdrawal includes detecting treatment fluid temperatures. In furthervariations of the foregoing embodiments, the regulating is responsive torespective temperatures of the at least two treatment fluids. In furthervariations of the foregoing embodiments, the regulating is responsive torespective flow rates of the at least two treatment fluids. In furthervariations of the foregoing embodiments, the regulating is responsive torespective flow rates and temperatures of the at least two treatmentfluids.

According to additional embodiments, the disclosed subject matterincludes a method of regulating blood return temperature in anextracorporeal blood treatment. The method includes actively regulatinga fluid temperature regulator power output, using feedback control basedon a blood return temperature signal, to control the temperature of asubset of multiple medicament streams the flow into, or contact, flowingblood. The method includes detecting a change in a flow rate ortemperature of any one of the multiple medicament streams. The methodincludes resetting a rate of the fluid temperature regulator poweroutput using feedforward control responsively to the detecting.

In variations of the foregoing embodiments, the method further includesreverting to the actively regulating using feedback control followingthe resetting. In further variations of the foregoing embodiments, thefeedforward control includes estimating a heat transfer occurring in ablood treatment device. In further variations of the foregoingembodiments, the method includes an initial resetting prior to theactively regulating using feedback control at the beginning of a bloodtreatment.

In further variations of the foregoing embodiments, the detecting achange in a flow or temperature of any one of the multiple medicamentstreams includes detecting a change in a rate of ultrafiltration.

In further variations of the foregoing embodiments, the subset is one ofthe multiple medicament streams.

According to embodiments, the disclosed subject matter includesapparatus for controlling flow in a fluid circuit. A treatment machine,having an extracorporeal blood processing function. The treatmentmachine having pump actuators each engageable with a respective fluidline of to pump a respective one of two or more treatment fluids. Thetreatment machine having a fluid temperature regulator that includes aheater or cooler that can be engaged with a fluid circuit to apply heatto a subset of the two or more treatment fluids. The treatment machinehas a controller with a venous temperature input that receives a bloodreturn temperature signal indicating a temperature of blood returning toa patient, a core temperature input that receives a core temperaturesignal indicating a core temperature of a patient undergoing treatment,and treatment fluid temperature inputs that receive respectivetemperatures of the two or more treatment fluids. The controller isconnected to the fluid temperature regulator to regulate a heatingand/or cooling output of the fluid temperature regulator. The controllercalculates and stores a target blood return temperature responsively tothe core temperature, the controller is programmed to regulate theheating and/or cooling output responsively to the stored target bloodreturn temperature by regulating the output of the fluid temperatureregulator to minimize a difference between the target blood returntemperature and a detected blood return temperature.

In further variations of the foregoing embodiments, the subset is asingle one of the two or more treatment fluids. In further variations ofthe foregoing embodiments, a heating and/or cooling effect of fluid inthe subset is generated by the temperature in the subset reachingequilibrium with the temperature of blood due to heat transfer ofadmixing.

According to embodiments, the disclosed subject matter includes a methodof regulating a blood return temperature during a blood treatment. Themethod includes withdrawing blood from a living subject andsimultaneously cooling and heating the blood by admixing of one or moreof at least two treatment fluids, withdrawing fluid from the blood, andtransferring heat between the blood and the one or more of the at leasttwo treatment fluids. The method includes returning the blood to theliving subject after the simultaneously heating and cooling anddetecting a temperature of the returning blood. The method includesusing the controller connected to receive a signal indicating thetemperature of the returning blood and responsively thereto, regulatinga rate of heat addition or withdrawal to, or from, a subset of the atleast two treatment fluids by means of a temperature regulatorcontrolled by the controller to achieve a predefined temperature of thereturning blood without actively heating or cooling others (than thesubset) of the at least two treatment fluids.

In further variations of the foregoing embodiments, the regulating arate of heat addition or withdrawal is responsive to respective flowrates of the at least two treatment fluids. In further variations of theforegoing embodiments, the regulating a rate of heat addition orwithdrawal is responsive to a combined effect of the simultaneouslycooling and heating. In further variations of the foregoing embodiments,the regulating a rate of heat addition or withdrawal is responsive to isrespective flow rates of the at least two treatment fluids. In furthervariations of the foregoing embodiments, the subset of the at least twotreatment fluids includes dialysate. In further variations of theforegoing embodiments, the subset includes a one of the at least twothat has a highest flow rate of all the at least two. In furthervariations of the foregoing embodiments, the regulating a rate of heataddition or withdrawal includes detecting treatment fluid temperatures.In further variations of the foregoing embodiments, the regulating isresponsive to respective temperatures of the at least two treatmentfluids. In further variations of the foregoing embodiments, theregulating is responsive to respective flow rates of the at least twotreatment fluids. In further variations of the foregoing embodiments,the regulating is responsive to respective flow rates and temperaturesof the at least two treatment fluids.

It will be appreciated that the modules, controllers, processes,systems, and sections described above can be implemented in hardware,hardware programmed by software, software instruction stored on anon-transitory computer readable medium or a combination of the above.For example, a method for balancing fluid flow can be implemented, forexample, using a processor configured to execute a sequence ofprogrammed instructions stored on a non-transitory computer readablemedium. For example, the processor can include, but not be limited to, apersonal computer or workstation or other such computing system thatincludes a processor, microprocessor, microcontroller device, or iscomprised of control logic including integrated circuits such as, forexample, an Application Specific Integrated Circuit (ASIC). Theinstructions can be compiled from source code instructions provided inaccordance with a programming language such as Java, C++, C#.net or thelike. The instructions can also comprise code and data objects providedin accordance with, for example, the Visual Basic™ language, LabVIEW, oranother structured or object-oriented programming language. The sequenceof programmed instructions and data associated therewith can be storedin a non-transitory computer-readable medium such as a computer memoryor storage device which may be any suitable memory apparatus, such as,but not limited to read-only memory (ROM), programmable read-only memory(PROM), electrically erasable programmable read-only memory (EEPROM),random-access memory (RAM), flash memory, disk drive and the like.

Furthermore, the modules, processes, systems, and sections can beimplemented as a single processor or as a distributed processor.Further, it should be appreciated that the steps mentioned above may beperformed on a single or distributed processor (single and/ormulti-core). Also, the processes, modules, and sub-modules described inthe various figures of and for embodiments above may be distributedacross multiple computers or systems or may be co-located in a singleprocessor or system. Exemplary structural embodiment alternativessuitable for implementing the modules, sections, systems, means, orprocesses described herein are provided below.

The modules, processors or systems described above can be implemented asa programmed general purpose computer, an electronic device programmedwith microcode, a hard-wired analog logic circuit, software stored on acomputer-readable medium or signal, an optical computing device, anetworked system of electronic and/or optical devices, a special purposecomputing device, an integrated circuit device, a semiconductor chip,and a software module or object stored on a computer-readable medium orsignal, for example.

Embodiments of the method and system (or their sub-components ormodules), may be implemented on a general-purpose computer, aspecial-purpose computer, a programmed microprocessor or microcontrollerand peripheral integrated circuit element, an ASIC or other integratedcircuit, a digital signal processor, a hardwired electronic or logiccircuit such as a discrete element circuit, a programmed logic circuitsuch as a programmable logic device (PLD), programmable logic array(PLA), field-programmable gate array (FPGA), programmable array logic(PAL) device, or the like. In general, any process capable ofimplementing the functions or steps described herein can be used toimplement embodiments of the method, system, or a computer programproduct (software program stored on a non-transitory computer readablemedium).

Furthermore, embodiments of the disclosed method, system, and computerprogram product may be readily implemented, fully or partially, insoftware using, for example, object or object-oriented softwaredevelopment environments that provide portable source code that can beused on a variety of computer platforms. Alternatively, embodiments ofthe disclosed method, system, and computer program product can beimplemented partially or fully in hardware using, for example, standardlogic circuits or a very-large-scale integration (VLSI) design. Otherhardware or software can be used to implement embodiments depending onthe speed and/or efficiency requirements of the systems, the particularfunction, and/or particular software or hardware system, microprocessor,or microcomputer being utilized. Embodiments of the method, system, andcomputer program product can be implemented in hardware and/or softwareusing any known or later developed systems or structures, devices and/orsoftware by those of ordinary skill in the applicable art from thefunction description provided herein and with a general basic knowledgeof controllers and especially digital controllers and/or computerprogramming arts.

Moreover, embodiments of the disclosed method, system, and computerprogram product can be implemented in software executed on a programmedgeneral purpose computer, a special purpose computer, a microprocessor,or the like.

It is, thus, apparent that there is provided, in accordance with thepresent disclosure, flow balancing devices, methods and systems. Manyalternatives, modifications, and variations are enabled by the presentdisclosure. Features of the disclosed embodiments can be combined,rearranged, omitted, etc., within the scope of the invention to produceadditional embodiments. Furthermore, certain features may sometimes beused to advantage without a corresponding use of other features.Accordingly, Applicants intend to embrace all such alternatives,modifications, equivalents, and variations that are within the spiritand scope of the present invention.

The invention claimed is:
 1. A method of regulating a blood returntemperature during a blood treatment, comprising: withdrawing blood froma living subject and flowing the blood through a blood treatment devicewith a membrane across which toxins and electrolytes pass between theblood and at least one treatment fluid of at least two treatment fluids;simultaneously cooling and heating the blood by admixing the blood witha second one of the at least two treatment fluids, withdrawing fluidfrom the blood in the blood treatment device, and transferring heatbetween the blood and the at least two treatment fluids; returning theblood to the living subject after said simultaneously heating andcooling and detecting a temperature of the returning blood; and using acontroller connected to receive a signal indicating said temperature ofthe returning blood and responsively thereto, regulating a rate of heataddition or withdrawal to or from one of the at least two treatmentfluids by a temperature regulator controlled by the controller toachieve a predefined temperature of the returning blood, wherein theusing the controller to regulate the rate of the heat addition orwithdrawal to or from said one of the at least two treatment fluidsincludes calculating a required power output of the temperatureregulator based at least on an ultrafiltration rate UF which representsa quantity of the fluid withdrawn from the blood, on a mass flow rate ofsaid one of the at least two treatment fluids flowing into the bloodtreatment device, and on a mass flow rate of the blood into the bloodtreatment device.
 2. The method of claim 1, wherein the regulating therate of the heat addition or withdrawal is responsive to respective flowrates of the at least two treatment fluids.
 3. The method of claim 1,wherein the regulating the rate of the heat addition or withdrawal isresponsive to a combined effect of said simultaneously cooling andheating.
 4. The method of claim 3, wherein the regulating the rate ofthe heat addition or withdrawal is responsive to is respective flowrates of the at least two treatment fluids.
 5. The method of claim 1,wherein the one of the at least two treatment fluids is a dialysate. 6.The method of claim 1, wherein the one of the at least two treatmentfluids has a higher flow rate than another of the at least two treatmentfluids.
 7. The method of claim 1, wherein the regulating the rate of theheat addition or withdrawal includes detecting treatment fluidtemperatures.
 8. The method of claim 1, wherein the regulating the rateof the heat addition or withdrawal is responsive to respectivetemperatures of the at least two treatment fluids.
 9. The method ofclaim 1, wherein the regulating the rate of the heat addition orwithdrawal is responsive to respective flow rates and temperatures ofthe at least two treatment fluids.
 10. The method according to claim 1,wherein the blood treatment device includes the membrane that separatestwo compartments, the blood flows through one of the two compartments,and the at least one treatment fluid flows through another of the twocompartments.
 11. The method according to claim 10, wherein thetransferring heat between the blood and the at least two treatmentfluids takes place in the blood treatment device.
 12. A method ofcontrolling a temperature of blood returning to a patient during a bloodtreatment, the method comprising: withdrawing the blood from the patientthrough an arterial access line; flowing the blood from the arterialaccess line into a first inlet port of a blood treatment device, along afirst side of a membrane inside the blood treatment device, and out of afirst outlet of the blood treatment device into a venous access linethat returns the blood to the patient; flowing a treatment fluid into asecond inlet port of the blood treatment device, along a second side ofthe membrane on an opposite side of the blood that is flowing throughthe blood treatment device, and out of a second outlet of the bloodtreatment device; during the flow of the blood and of the treatmentfluid exchanging heat between the blood and the treatment fluid;measuring a temperature of the blood in the venous access line; applyingpower to a temperature regulator which is configured to heat or cool thetreatment fluid before the treatment fluid flows through the bloodtreatment device; and controlling the applying of the power with acontroller which is configured to calculate a required power output ofthe temperature regulator based at least on an ultrafiltration rate UF,which is a difference between flows in the arterial access line and thevenous access line, on a first mass flow rate of the treatment fluidflowing into the second inlet port, and on a second mass flow rate ofthe blood flowing into the first inlet port.
 13. The method according toclaim 12, wherein the treatment fluid is a dialysate.
 14. The method ofclaim 12, wherein the controlling the applying of the power with thecontroller includes detecting a temperature of the treatment fluid.